International Journal of Hematology

, Volume 105, Issue 3, pp 235–243 | Cite as

The initiation and effects of plasma contact activation: an overview

  • Lisha Lin
  • Mingyi Wu
  • Jinhua Zhao
Review Article


The plasma contact system sits atop the intrinsic coagulation cascade and plasma kallikrein–kinin pathway, and in vivo its activation contributes, respectively, to coagulation and inflammation mainly via two downstream pathways. This system has been widely investigated, its activation mechanisms by negatively charged surfaces and the interactions within its components, factor XII, prekallikrein and high molecular weight kininogen are well understood at the biochemical level. However, as most of the activators that have been discovered by in vitro experiments are exogenous, the physiological activators and roles of the contact system have remained unclear and controversial. In the last two decades, several physiological activators have been identified, and a better understanding of its roles and its connection with other signaling pathways has been obtained from in vivo studies. In this article, we present an overview of the contact pathway with a focus on the activation mechanisms, natural stimuli, possible physiological roles, potential risks of its excessive activation, remaining questions and future prospects.


Contact activation Kallikrein–kinin Coagulation Inflammation Factor XII 



Factor XII


Factor XI




High molecular weight kininogen






Kinin B1 receptors


Kinin B1 receptors




Urokinase-type plasminogen activator receptor


Globular heads of complement C1q




Heat shock protein 90


Factor VII


Tissue factor


Activated partial prothrombin time


Activated coagulation time


Hereditary angioedema


C1 inhibitor


Oversulfated chondroitin sulfate



This work was funded in part by the Yunnan Provincial Science and Technology Department in China (2010CI116, 2013FA046, and 2012FB177), National Natural Science Foundation of China (81102372, 81373292 and 81673330), and Institutes for Drug Discovery and Development, Chinese Academy of Sciences(CASIMM0220151008).

Compliance with ethical standards

Conflict of interest

The authors state that they have no conflict of interest.


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Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  1. 1.State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Pharmaceutical Chemistry, Kunming Institute of BotanyChinese Academy of SciencesKunmingChina
  2. 2.University of Chinese Academy of SciencesBeijingChina

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